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| 乌司他丁对大鼠机械通气肺损伤时γ-氨基丁酸信号通路的影响 |
| Effect of ulinastatin on γ-aminobutyric acid signal pathway in mice with ventilator-induced lung injury |
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| DOI： |
| 中文关键词: γ-氨基丁酸信号通路 乌司他丁 机械通气肺损伤 呼吸窘迫综合征 |
| 英文关键词: γ-Aminobutyric acid signaling pathway Ulinastatin Ventilator-induced lung injury Respiratory distress syndrome |
| 基金项目:国家自然科学基金(81571936,81401626);江苏省“六大人才高峰”（WSW-077) |
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| 中文摘要: |
| 目的 探讨乌司他丁对大鼠机械通气引起的呼吸机相关性肺损伤（ventilator-induced lung injury,VILI）时γ-氨基丁酸(GABA)信号通路的影响。方法 选取健康成年雄性Wister大鼠36只,采用随机数字表法分为三组:正常对照组(C组)、机械通气肺损伤组(VILI组)和机械通气肺损伤+乌司他丁处理组(UTI组)，每组12只。VILI组与UTI组采用VT 40 ml／kg机械通气4 h的方法制备大鼠VILI模型。机械通气前1 h,UTI组腹腔注射乌司他丁1×105 U／kg,C组和VILI组给予等容量生理盐水。收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),检测BALF中白细胞介素-1β(interleukin-1β, IL-1β)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)及细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)的浓度;取肺组织,检测湿／干重比(W／D)、肺组织IL-1β、TNF-α和ICAM-1 mRNA的表达;采用免疫组化与Western blot法检测肺组织GAD与GABAA受体的表达量,观察病理学结果并进行肺损伤评分。结果 与VILI组比较,UTI组W／D (6.7±2.4 vs. 8.5±2.3)、肺损伤评分［(6.9±2.3)分 vs. (11.8±2.7)分］明显降低(P＜0.05);BALF中IL-1β［(56±11)ng／L vs. (77±15) ng／L］、TNF-α［(105±29) ng／L vs. (158±37) ng／L］及ICAM-1［(205±46) ng／L vs. (293±61) ng／L］浓度明显降低(P＜0.05);肺组织IL-1β(1.81±0.26 vs. 2.58±0.34)、TNF-α (1.61±0.15 vs. 2.94±0.27)、ICAM-1 (1.74±0.27 vs. 2.79±0.31) mRNA表达量明显降低(P＜0.05);GAD (0.44±0.08 vs. 0.18±0.04)和GABAA (0.30±0.09 vs. 0.15±0.04)受体表达量明显增加(P＜0.05)。结论 乌司他丁可减轻大鼠机械通气引起的呼吸机相关性肺损伤,其机制可能与激活γ-氨基丁酸信号通路有关。 |
| 英文摘要: |
| Objective To evaluate the effect of ulinastatin on γ-aminobutyric acid (GABA) signal pathway in mice with ventilator-induced lung injury (VILI). Methods Thirty-six male Wister mice were randomly divided into 3 groups using a random number table: control group (group C), ventilator-induced lung injury group (group VILI), and ventilator-induced lung injury+ulinastatin group (group UTI), n=12 in each group. VILI was induced by 4 h mechanical ventilation with tidal volume 40 ml/kg in groups VILI and UTI. Ulinastatin 1×105 U/kg was injected intraperitoneally 1 h before ventilation in group UTI, while the equal volume of normal saline was given in groups C and VILI. The mice were then sacrificed, the left lung was lavaged, and broncho-alveolar lavage fluid (BALF) was collected for determination of concentrations of protein,tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and intercellular adhesion molecule-1 (ICAM-1). The lung tissues were removed for determination of the wet to dry lung weight (W/D) ratio, the mRNA expression level of IL-1β, TNF-α and ICAM-1. The pathological changes of the lungs were determined under light microscope and the lung injury scores were also determined. Immunohistochemistry and Western blot were used to detected the protein expression level of GAD and GABAAR. Results The W/D ratio (6.7±2.4 vs. 8.5±2.3) and lung scores [(6.9±2.3) scores vs. (11.8±2.7) scores] were significantly decreased in group UTI than those in group VILI. The concentrations of IL-1β [(56±11) ng/L vs. (77±15) ng/L], TNF-α [(105±29) ng/L vs. (158±37) ng/L] and ICAM-1 [(205±46) ng/L vs. (293±61) ng/L] in BALF in group UTI were significantly decreased than those in group VILI. The mRNA expression levels of IL-1β (1.81±0.26 vs. 2.58±0.34), TNF-α (1.61±0.15 vs. 2.94±0.27) and ICAM-1 (1.74±0.27 vs. 2.79±0.31) were significantly decreased in group UTI than those in group VILI. The protein expression levels of GAD (0.44±0.08 vs. 0.18±0.04) and GABAAR (0.30±0.09 vs. 0.15±0.04) were significantly increased in group UTI than those in group VILI. Conclusion Ulinastatin can attenuate VILI probably through activating GABA signaling pathway. |
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